It is known that CoQ10—liposoluble substance—has been introduced into the clinical practice in Japan for patients having cardiac disorders and, in addition, it is presently used for a wide range of disorders and pathologies. For example, CoQ10 in combination with statins improves the haematochemical profile (cholesterol, HDL and nitric oxide levels), in the mitochondrial myopathies it improves the clinical picture, normalizing levels of lactate and creatine kinase, in the neurodegenerative diseases it showed encouraging results on key biochemical parameters of Parkinson's disease and, finally, in patients often suffering from migraine, it reduces the frequency of attacks and the days with headache and nausea. Moreover, CoQ10 may be useful in association with the conventional therapies, since, due its metabolic role, it may positively influence the progression of many diseases or it may prevent their onset. As an example, the antioxidant properties of CoQ10 in the cardiovascular disorders may end up being crucial in blocking the action of free radicals, which are responsible of dysfunctions in the endothelial tissue.
There are various techniques to provide formulations of CoQ10 as orally administrable forms. For example, the following scientific papers are available “Emulsification of coenzyme Q10 using gum arabic increases bioavailability in rats and human and improve food processing suitability” in J. Nutr. Sci. Vitaminol. 56, 41-47, 2010 and “Improvement of the oral bioavailability of coenzyme Q10 by emulsification with fats and emulsifiers used in the food industry” LWT-Food Science and Technology 42 (2009) 385-390.
In Onoue et al. (“Novel solid self-emulsifying drug delivery system of coenzyme Q10 with improved photochemical and pharmacokinetic behaviour”, European Journal of Pharmaceutical Sciences 46 (2012) 492-499), a drug transport and delivery system of the solid auto emulsifying type (SEDDS) is described. In particular, a preformed emulsion containing CoQ10, as liposoluble active ingredient, MCT (Medium Chain Triglyceride), as oily phase, fatty acids sucrose ester as tensioactive agent, and hydroxypropylcellulose (HPC), as solid carrier, is spray-dried. In particular, the starting emulsion is prepared by pre-solubilizing CoQ10 (5 g), MCT (5 g) and sucrose ester (40 g) in ethanol (500 ml) and emulsifying this solution with HPC (50 g) dissolved in water (1,500 ml). Such liquid suspension is atomized in spray drops, thus obtaining a CoQ10/s-SEDDS system, wherein the macroscopic morphology is that of aggregated spherical particles, in which CoQ10 is present predominantly in form of dispersed particles and platelets, having a size from about 5 to 50 micrometers.
In this field the following patent applications are also available: EP-A-1782803, GB-A-2402334, US-A-2007/202166, US-A-2008/248013, US-A-2009/054530, US-A-2009/186009, WO-A-02/067864, WO-A-98/03170, WO-A-2007/086689 and CN-A-101940564 or CN-A-101172102.
However, for the above formulations the solution profiles have never been reported either due to their oily nature and poor hydrosolubility or due to the absence of a suitable dissolution medium. Moreover, such approaches result in long and expensive procedures, which often require the use of solvents or solvent mixtures, which have to be removed to obtain a solid system and traces of which may remain in the final product. In alternative, such procedures may require the use of high temperatures, which may risk degrading the final product.
Finally, in many such procedures it is necessary to use more than three components to obtain the desired result or high concentrations of surfactants or carriers, which limit the content of CoQ10 to very low levels.
In the attempt to solve the technical problems relating to the preparation of compositions in the form of fine powders comprising active ingredients substantially poorly soluble in water and organic solvents, a process of dry co-grinding has been described in the International patent application WO-A-03/097012 (WO'012), wherein an active ingredient is included in a hydrophilic or hydrophobic carrier, depending on the chemical-physical characteristics of the active ingredient, in the presence of a co-grinding auxiliary substance, which allows a drastic reduction of the co-grinding time with indisputable advantages for the stability of the active ingredient.
The international patent application WO-A-07/009997 (WO'997) describes the application of such technique to antioxidant agents, including CoQ10 to obtain compositions in form of fine powder easily dispersible and possibly soluble in water, which have shown significant increase in antioxidant power for the same concentration of active ingredient in solution.
The international patent application WO-A-2013/080028 (WO'028) describes a composition based on ubidecarenone, consisting of CoQ10, one or more specific carriers selected from the group of maltodextrins and one or more adjuvant agents selected from the group of sucrose esters. In WO'028 examples of compositions based on ubidecarenone are also reported, which consist of CoQ10, hydroxypropylmethyl cellulose (HPMC) and one or more adjuvant agents selected from the group of sucrose esters. However, such compositions are described in WO'028 as less performing than those containing maltodextrins due to their lower solubility and the jellifying capability of the carrier hydroxypropylmethyl cellulose.
Therefore, there is in the field the consistent need to provide a composition based on CoQ10 together with its preparation method, which, on one hand, could improve the solubility and dissolution of CoQ10, and on the other hand could be prepared in an efficient, rapid and economical way.
There is, therefore, a need to improve a composition based on CoQ10, which could overcome at least one of the disadvantages of the state of the art.
In particular, a purpose of the present invention is to provide a new composition based on CoQ10 and to develop a method for its preparation, which allows obtaining a high solubility and dissolution of CoQ10.
To obviate the drawbacks of the state of the art and to obtain these and further advantages, the Applicant has now considered, implemented and tested the present invention.
Unless otherwise indicated, all the technical and scientific terms used here and hereafter have the same meaning commonly understood by a person having ordinary skill in the art, to which the present invention belongs. Even if methods and materials similar or equivalent to those herein described maybe used in the practice or in the tests of the present invention, hereinafter materials and methods are described as examples. The materials, methods and examples have purely illustrative purposes and must not be construed in a limitative way.
The word “to comprise” and variants of the word, such as “comprises” and “comprising” are used here to indicate the inclusion of a clearly expressed whole or clearly expressed wholes, but not the exclusion of any other whole or any other wholes, unless in the context or in use an exclusive interpretation of the word is required.
The word “to consist” and variants of the word, such as “consists” and “consisting” are used here to indicate the inclusion of a clearly expressed whole or clearly expressed wholes and the exclusion of any other whole or any other wholes.